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Biomedical subjects

L G Navar

Publications and source records attributed to L G Navar.

At least 181 records · Page 10Linked to original sources
PubMed1982

Role of a macula densa feedback mechanism as a mediator of renal autoregulation.

The phenomenon of renal autoregulation demonstrates the presence of a sensitive intrarenal mechanism capable of maintaining GFR stable even during extrinsic disturbances that would be expected to alter renal hemodynamics. Substantial evidence has accumulated indicating that autoregulatory capability is dependent on the integrity of normal distal tubule flow dynamics and an intact distal tubuloglomerular feedback mechanism. Several whole-kidney and micropuncture studies have shown that interruption of volume delivery to the distal nephron interferes with autoregulation of renal blood flow (RBF) and GFR. The autoregulatory adjustments are probably localized at the afferent arterioles because the pressure in the larger arterioles does not exhibit autoregulation in response to decreases in renal perfusion pressure. It remains uncertain if the distal tubuloglomerular feedback mechanism is entirely responsible for autoregulatory responses. Data obtained in dog experiments indicate that under conditions of interrupted delivery to the distal nephron, SNGFR responses to decreases in arterial pressure are approximately those expected of a passive system where proximal tubule pressure is allowed to adjust to new steady-state levels with regard to the rapidity with which signals are transmitted to the distal nephron. Whole-kidney experiments indicate that, under conditions of a mild osmotic diuresis, the changes in urine flow following an increase in arterial pressure occur within 1 sec of the initiation of autoregulatory adjustments in vascular resistance. These experiments are consistent with the view that the major fraction of renal autoregulatory adjustments in resistance is mediated by the distal tubuloglomerular feedback mechanism that responds to some component of distal tubular flow and transmits signals to the afferent arteriolar segment of the same nephron.

Animals↗
PubMed1981

Hemodynamic and single nephron function during the maintenance phase of ischemic acute renal failure in the dog.

We studied ischemic acute renal failure in 28 dogs by micropuncture, microsphere, morphologic, and whole kidney hemodynamic techniques, 18 to 24 hours after the renal artery was clamped (clamping time, 60 to 90 min). Before the artery was clamped, renal blood flow (RBF) averaged 3.49 +/- (SEM) 0.23 ml/min x g and was not significantly different (3.70 +/- 0.34 ml/min x g) 18 hours after the ischemic episode. RBF autoregulatory capability was, however, significantly reduced. Fractional outer cortical blood flow decreased slightly from 41 +/- 2 to 36 +/- 3% (P less than 0.05) postischemia. Single nephron glomerular filtration rate (SNGFR) was highly variable from one animal to the next and ranged from 0 to 87 nl/min (mean, 36 +/- [SEM] 7 nl/min) in a manner similar to whole kidney inulin clearance, which ranged from 0 to 0.56 ml/min x g (mean, 0.30 +/- 0.05 ml+min x g). The correlation coefficient between SNGFR and inulin clearance was highly significant, indicating an association between SNGFR and whole kidney GFR. Proximal tubule pressure (PTP) averaged 20 +/- (SEM) 1 mm Hg. In 6 dogs, the glomerular filtration coefficient (Kf) was determined by measurements of stop-flow pressure, colloid osmotic pressure, SNGFR, PTP, and single nephron filtration fraction, Kf was below that obtained for control animals. Scanning electron microscopy (SEM) studies indicated that the endothelial fenestrations were reduced in number and size. These studies suggest that one major characteristic of ischemic nephropathy in the dog is a derangement in the filtration process. The maintenance of RBF in the postischemic phase may occur by utilization of the autoregulatory reserve of the renal vasculature.

Acute Kidney Injury↗
PubMed1981

Dissociation of tubuloglomerular feedback responses from distal tubular chloride concentration in the rat.

Previous studies have demonstrated that stop-flow pressure (SFP) feedback responses can occur during orthograde perfusion with solutions having low amounts of sodium or chloride. However, retrograde perfusion studies have suggested a specific role for chloride concentration in mediating feedback responses. These studies were conducted to compare SFP feedback responses during orthograde and retrograde perfusion with an artificial tubular fluid solution (ATF) (Cl- = 135 meq/liter) and a Na+ isethionate solution (Cl- = 6 meq/liter). With ATF, increases in perfusion rate from 10 to 35 nl/min led to decreases in SFP of 11 +/- 1.4 mmHg, increases in distal tubular fluid Cl- of 46 +/- 4.9 meq/liter, and osmolality of 58 +/- 10 mosmol/kg. There were significant inverse relationships between SFP and changes in Cl- and osmolality. With Na+ isethionate, SFP decreased by 8.4 +/- 1.0 mmHg, osmolality increased by 43 +/- 8 mosmol/kg, and Cl- did not change. There was a significant relationship between SFP and osmolality, but not with Cl-. During retrograde perfusion at 15 nl/min, SFP decreased by 12 +/- 1.2 mmHg with ATF and by 12 +/- 1.2 mmHg with Na+ isethionate. These results demonstrate that feedback-mediated decreases in SFP can occur in the absence of concomitant increases in distal Cl- and suggest that the receptor system does not have a unique and specific requirement for chloride.

Animals↗
PubMed1981

Role of feedback mechanism in renal autoregulation and sensing step in feedback pathway.

The unique morphology of the juxtaglomerular complex has resulted in many investigations evaluating its potential physiological roles. One hypothesis that has stimulated considerable interest is that feedback signals originating from distal tubule cells, presumably at the macula densa segment, participate in the phenomenon of renal autoregulation. Data obtained from dog experiments indicate tha autoregulation of single nephron glomerular filtration rate (SNGFR) is most consistently observed when fluid delivery to the early distal tubule is not interrupted. In contrast, techniques that interfere with normal orthograde fluid delivery to the distal nephron have usually resulted in increases in SNGFR and an inability to exhibit appropriate autoregulatory responses to decreases in arterial pressure. There is considerable uncertainty concerning the nature of the intraluminal component of the early distal tubule fluid responsible for initiating feedback responses. The studies reported in this paper have indicated that feedback mediated decreases in stop-flow pressure and SNGFR in response to increases in distal microperfusion rate can occur with a variety of artificial perfusion solutions, including solutions that contain low concentrations of chloride, sodium, or total electrolytes. Microperfusion studies in the rat have demonstrated that feedback mediated decreases in stop-flow pressure can occur in the absence of associated increases in distal tubule fluid chloride concentration. These results are consistent with the concept that some function of distal tubule fluid osmolality or distal tubule solute delivery may participate in the initiation of feedback signals.

Animals↗
PubMed1980

Impaired renal blood flow autoregulation in ischemic acute renal failure.

We used a model of ischemic acute renal failure featuring normal renal blood flow (RBF) to evaluate the autoregulatory capability in a preparation having a marked reduction of inulin clearance (GFR). In 10 dogs, we clamped the renal artery for 90 min (experimental); 6 dogs, 1 min only (sham). Approximately 18 hours later, we determined the autoregulatory ability from RBF responses to renal arterial constriction. GFR of the experimental dogs was 10 +/- 4 ml/min, significantly lower than GFR in the sham dogs (43 /+- 9 ml/min). RBF in the experimental dogs (189 +/- 17 ml/min) was not significantly different from that in the sham dogs (206 +/- 32). An autoregulation index, ranging from 0.49 to 1.09 (mean 0.690), was significantly larger than was that of sham dogs, which ranged from zero to 0.23 (mean 0.060). At control arterial pressures, vascular resistance was comparable in both groups; however, at reduced arterial pressures below the normal autoregulatory range, average resistance of the experimental dogs (0.62 +/- 0.12 mm Hg/[ml/min]) was significantly greater than was that of the sham dogs (0.38 +/- 0.06 mm Hg/[ml/min]). These studies indicate that a substantial loss of renal hemodynamic responsiveness follows ischemic injury to the dog even when RBF is maintained within the normal range. The loss of autoregulatory capacity associated with a severely attenuated GFR is consistent with a role for tubular flow in the normal mechanism of autoregulation.

Acute Kidney Injury↗
PubMed1980

Impaired autoregulatory responses in contralateral kidneys of two-kidney, one-clip hypertensive rats.

1. Micropuncture and clearance experiments in two-kidney, one-clip renal vascular hypertensive rats examined the ability of the kidney contralateral to renal vascular stenosis to maintain renal function during conditions of reduced renal arterial blood pressure. 2. At their respective spontaneous blood pressures, renal vascular resistance was higher and glomerular filtration rate (GFR) and renal blood flow were not different in the contralateral kidneys of the hypertensive rats (170 +/- 5 mmHg) compared with normal animals (129 +/- 1 mmHg). Urine flow and absolute and fractional excretion of electrolyte were greater from the kidneys of the hypertensive animals. However, pressures in cortical structures were similar in the two groups. 3. As blood pressure was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in renal vascular resistance that failed to allow GFR, renal blood flow or pressures in cortical structures to be maintained. In contrast, normal rats efficiently autoregulated renal vascular resistance to allow GFR, renal blood flow and cortical pressures to be unchanged as blood pressure was altered between 130 and 115 mmHg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys; at comparable blood pressure these indices of excretory function were not different in the two groups. 4. These observations indicate that the contralateral kidney can maintain normal haemodynamic and glomerular function only at elevated blood pressure and suggest the possibility that the impaired capacity to autoregulate renal resistances may contribute to the maintenance of hypertension observed in this model.

Animals↗
PubMed1979

Glomerular filtration dynamics in the dog during elevated plasma colloid osmotic pressure.

To determine if the glomerular filtration coefficient (Kf) of the dog is influenced by changes in plasma colloid osmotic pressure (COP), we conducted micropuncture experiments in dogs given concentrated albumin solutions. In one group (N = 9), filtration dynamics were evaluated following infusion of 450 to 600 ml of a 25% bovine albumin solution. To minimize the effects of acute volume expansion, we also achieved high COP levels in another group (N = 7) by albumin loading on the day prior to the experiment. In all experiments, renal arterial pressure was reduced to approximately 90 mm Hg to minimize potential errors that might lead to overestimation of single nephron filtration rate (SNGFR) and glomerular pressure (GP). In the acutely expanded dogs, COP increased to 23.0 +/- (SEM) 0.9 mm Hg, SNGFR was 59 +/- 6 nl/min, estimated GP was 61.0 +/- 2.0 mm Hg, proximal tubule pressure (PTP) was 23.0 +/- 1.6 mm Hg, and superficial filtration fraction (SFF) was 0.13 +/- 0.02. A similarly reduced whole kidney filtration fraction was also observed, due almost entirely to a marked increase in renal blood flow. When compared to noninfused control dogs (N = 13), Kf was significantly higher in the dogs with elevated COP, being 5.3 +/- 0.6 nl/min/mm Hg as compared to 3.4 +/- 0.3 nl/min/mm Hg. Average effective filtration pressure (EFP) was 12 +/- 1mm Hg, and EFP at the efferent end of the glomerular capillaries was 8.9 +/- 1.2 mm Hg. In the group infused on the prior day, COP was 20.0 +/- 0.8 mm Hg, SFF was 0.26 +/- 0.01, SNGFR was 70 +/-8 nl/min, GP was 59 +/- 2 mm Hg, and PTP was 19.0 +/- 1.5 mm Hg. Average EFP was 15 +/- 1 mm Hg, and EFP at the efferent end of the capillaries was 7.5 +/- 0.7 mm Hg. kf was 4.85 +/- 0.66 nl/min/mm Hg, a value significantly higher than that obtained in control dogs having a COP of 15.0 +/- 0.6 mm Hg. Furthermore, one group of control dogs (N = 4), expanded with an isooncotic albumin solution, did not exhibit significant changes in Kf even though the degree of plasma volume expansion was similar to the group expanded with concentrated albumin solution. These experiments are consistent with previous findings obtained in the rat that Kf is influenced by the COP, although the changes in Kf appear to be less than they are in the rat. The data indicate that even under these conditions of elevated COP, the filtration process in the dog is characterized by positive filtration pressures throughout the length of the glomerular capillaries.

Albumins↗
PubMed1979

Tubuloglomerular feedback and single nephron function after converting enzyme inhibition in the rat.

Experiments were done in normal rats to assess kidney, single nephron, and tubuloglomerular feedback responses during renin-angiotensin blockade with the converting enzyme inhibitor (CEI) SQ 20881 (E. R. Squibb & Sons, Princeton, N. Y.) (3 mg/kg, per h). Converting enzyme inhibition was documented by complete blockade of vascular responses to infusions of angiotensin I (600 ng/kg). Control plasma renin activity was 12.5+/-2.7 ng angiotensin I/ml per h (mean+/-SEM) and increased sevenfold with CEI (n = 7). There were parallel increases in glomerular filtration rate from 1.08+/-0.05 to 1.26+/-0.05 ml/min and renal blood flow from 6.7+/-0.4 to 7.5+/-0.5 ml/min. During CEI infusion absolute and fractional sodium excretion were increased 10-fold. Proximal tubule and peritubular capillary pressures were unchanged. Single nephron glomerular filtration rate (SNGFR) was measured from both proximal and distal tubule collections; SNGFR based only on distal collections was significantly increased by CEI. A significant difference was observed between SNGFR values measured from proximal and distal tubule sites (6.0+/-1.6 nl/min) and this difference remained unchanged after CEI administration. Slight decreases in fractional absorption were suggested at micropuncture sites beyond the late proximal tubule, whereas early distal tubule flow rate was augmented by CEI. Tubuloglomerular feedback activity was assessed by measuring changes in proximal tubule stop-flow pressure (SFP) or SNGFR in response to alterations in orthograde microperfusion rate from late proximal tubule sites. During control periods, SFP was decreased 11.2+/-0.4 mm Hg when the perfusion rate was increased to 40 nl/min; during infusion of CEI, the same increase in perfusion rate resulted in a SFP decrement of 6.7+/-0.5 mm Hg (P<.001). When late proximal tubule perfusion rate was increased from 0 to 30 nl/min, SNGFR was decreased by 15.0+/-1.2 nl/min during control conditions, and by 11.3+/-1.3 nl/min during CEI infusion. Attenuation of feedback responsiveness during CEI was also observed at lower perfusion rates with both techniques. These results indicate that blockade of the renin-angiotensin system with CEI reduces the activity of the tubuloglomerular feedback mechanism which may mediate the observed renal vasodilation.

Angiotensin I↗
PubMed1978

Filtration rate and stop-flow pressure feedback responses to nephron perfusion in the dog.

Experiments were performed to evaluate the influence of the distal tubular feedback mechanism on glomerular function in the dog. Single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) were measured from early segments of proximal tubules during alterations in distal perfusion rate (via a late proximal puncture site) and perfusate composition. Perfusion rate (PR) was varied from 16 to 68 nl/min with a microperfusion pump. The intermediate segment of the nephron was blocked with a solid wax cast, thus preventing retrograde influences of the microperfusion procedure. During perfusion with an ultrafiltrate of plasma and an artificial tubular fluid solution (ATF), SNGFR decreased from 63 +/- 2.6 (SE) nl/min at a PR of 16 nl/min to 20 +/- 2.4 nl/min at a PR of 63 +/- 2.6 nl/min. At a PR of 16 nl/min, SFP was 48 +/- 1.3 mmHg with ultrafiltrate and ATF. Increases in PR to 68 nl/min led to a reduction in SFP to 26 +/- 1.5 mmHg. SFP was also measured during changes in PR with various electrolyte solutions of decreasing complexity. Elimination or substitution of Na+, K+, Cl-, HCO3-, and Ca2+ did not significantly alter the magnitude of the feedback response to increases in PR to 68 nl/min. These results confirm the existence of a feedback system in the dog capable of adjusting glomerular function in response to changes in distal perfusion rate. The results based on the various perfusion solutions fail to indicate a unique requirement for any specific component.

Animals↗
PubMed1978

Renal autoregulation: perspectives from whole kidney and single nephron studies.

The phenomenon of renal autoregulation is often thought to relate only to the manner in which the kidney responds to changes in arterial pressure. This review presents a more comprehensive description of the process based on the intrinsic renal vascular responses to changes in arterial pressure, venous pressure, ureteral pressure, and plasma colloid osmotic pressure. Regulation of glomerular filtration rate (GFR), or some function thereof, is the feature most consistently observed. More specifically, in response to external manipulations that change GFR, autonomous changes in renal vascular resistance tend to return GFR back towards normal. The bulk of the evidence suggests that the requisite renal vascular resistance alterations occur predominately at preglomerular segments. Most of the whole kidney autoregulatory responses can be explained on the basis of the distal tubule-glomerular feedback hypothesis, thought to be mediated by the macula densa-juxtaglomerular complex, which states that increases in distal volume delivery lead to increases in afferent arteriolar resistance while reduced distal delivery leads to afferent arteriolar dilation. Micropuncture data have demonstrated that interruption of distal volume delivery prevents single nephrons from autoregulating GFR and glomerular pressure. Also, single nephron glomerular filtration rate (SNGFR) based on proximal collections is higher than SNGFR measured by distal collections or with an indicator-dilution technique. Studies utilized direct microperfusion of the distal nephron from a late proximal tubule site have demonstrated that SNGFR and glomerular pressure decrease in response to increases in distal nephron perfusion rate. Although experiments in rats have been interpreted as indicating that distal chloride concentration and/or reabsorption most likely mediate the feedback responses, recent studies in dogs have demonstrated that feedback responses can be consistently obtained with nonelectrolyte perfusion solutions. These latter studies suggest that the feedback response may be sensitive to some function of total solute delivery or concentration. At present, there is no clear understanding of the intracellular events that link the compositional alterations occurring within the early distal tubule to the final effector system.

Animals↗